According to the literature, the frequency of mutations in genes associated with the development of acute myeloid leukemia (AML) varies significantly.

The objective of this study was to obtain up-to-date data on the prevalence of mutations in the "hot spots" of the FLT3, NPM1, IDH1, IDH2, and DNMT3A genes in AML.

Methods: An analysis of NGS data from 1567 patients with AML presented in the cancer genomics database on C-Bioportal and 124 Russian patients with AML was performed.

Results: According to the database analysis, at the time of the diagnosis of the disease, 46.6% of patients had mutations in DNMT3A p.R882, NPM1 p.W288Cfs*12, FLT3-ITD, FLT3-TKD1, IDH1 p.R132, and IDH2 p.R140. Only in a third of cases (30.1%) did the DNMT3A mutation of R.R882 occur in patients in an isolated variant. In 47.4% of cases, it was combined with NPM1 p.W288Cfs*12, in 34.1% with mutations in the hot spots of the FLT3 gene, and in 23.0% with recurrent mutations in IDH1 and IDH2. At the same time, the combination revealed by our data remains highly significant (p<0.001) even after adjusting for the multiplicity of comparisons (q<0.001). In Russian AML patients, the mutation rates in the "hot spots" of genes generally corresponded to the data from the C-Bioportal cancer genomics database and amounted to the following: DNMT3A p.R882—7.3%; NPM1 p.W288Cfs*12—15.3%; FLT3-ITD—14.5%; FLT3-TKD1—4.0%; IDH1 p.R132—5.6%; IDH2 p.R140—10.5%.

Conclusions: The data obtained indicate that in 40-50% of AML cases, clinically significant recurrent mutations in one or more of the studied genes are detected at the onset of the disease. Mutations for which targeted drugs (FLT3, IDH1, and IDH2 inhibitors) have been developed occur in 35% of patients. In one-fifth of cases (18.1%) of AML, NPM1 p.W288Cfs*12 is detected, which can be used as an independent target for the molecular assessment of minimal residual disease.